Home LiteratureArticle Details
PMID: 8458320 Published · ppublish English Journal Article

Wild-type p53 adopts a 'mutant'-like conformation when bound to DNA.

The EMBO journal ·Vol. 12 ·No. 3 ·1993-03-00 ·Pages 1021-8

Halazonetis TD, Davis LJ, Kandil AN

Abstract

p53 is a negative regulator of cell growth. The majority of human tumors express mutant p53 proteins, which can be distinguished from wild-type by their immuno-reactivity to a panel of conformation-specific monoclonal antibodies, such as PAb421, PAb1620 and PAb246. Wild-type p53 has sequence-specific DNA binding activity. We demonstrate that upon binding DNA wild-type p53 changes conformation at both its N- and C-termini, such that it adopts a 'mutant'-like conformation. Very few of the known DNA binding proteins exhibit long-range conformational changes upon binding to DNA. Such proteins, like the Drosophila heat shock transcription factor, have DNA binding domains whose activity is regulated by conformation. The DNA binding activity, and therefore the function, of wild-type p53 may be regulated via its ability to adopt distinct conformations.

MeSH Terms
Animals Antibodies, Monoclonal Base Sequence Cells, Cultured DNA/metabolism Molecular Sequence Data Mutation Protein Binding Protein Conformation Rats Tumor Suppressor Protein p53/chemistry,genetics,metabolism
Chemicals
Antibodies, Monoclonal Tumor Suppressor Protein p53 DNA
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Halazonetis T D
Department of Cancer Research, Merck Research Laboratories, West Point, PA 19486.
Davis L J
Kandil A N
References (54)
54 references, click to expand
  1. Temperature-dependent switching between "wild-type" and "mutant" forms of p53-Val135.
    J Mol Biol. 1990 Dec 5;216(3):481-4 PMID: 2258922
  2. TP53 tumor suppressor gene: a model for investigating human mutagenesis.
    Genes Chromosomes Cancer. 1992 Jan;4(1):1-15 PMID: 1377002
  3. Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene.
    Science. 1990 Aug 31;249(4972):1049-51 PMID: 2144364
  4. Inhibition of p53 transactivation required for transformation by adenovirus early 1B protein.
    Nature. 1992 May 7;357(6373):82-5 PMID: 1533443
  5. T antigen is bound to a host protein in SV40-transformed cells.
    Nature. 1979 Mar 15;278(5701):261-3 PMID: 218111
  6. The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines.
    Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5523-7 PMID: 1648218
  7. The p53 tumour suppressor gene.
    Nature. 1991 Jun 6;351(6326):453-6 PMID: 2046748
  8. An enhancer "core" DNA-binding and transcriptional activity is induced upon transformation of rat embryo fibroblasts.
    Anticancer Res. 1992 Mar-Apr;12(2):285-91 PMID: 1580545
  9. Mutant p53 proteins bind DNA abnormally in vitro.
    Oncogene. 1991 Jan;6(1):131-6 PMID: 1846954
  10. c-Jun dimerizes with itself and with c-Fos, forming complexes of different DNA binding affinities.
    Cell. 1988 Dec 2;55(5):917-24 PMID: 3142692
  11. Different forms of p53 detected by monoclonal antibodies in non-dividing and dividing lymphocytes.
    Nature. 1984 Jul 12-18;310(5973):143-5 PMID: 6377090
  12. Wild-type p53 can inhibit oncogene-mediated focus formation.
    Proc Natl Acad Sci U S A. 1989 Nov;86(22):8763-7 PMID: 2530586
  13. A transcriptionally active DNA-binding site for human p53 protein complexes.
    Mol Cell Biol. 1992 Jun;12(6):2866-71 PMID: 1588974
  14. Cellular localization and cell cycle regulation by a temperature-sensitive p53 protein.
    Genes Dev. 1991 Feb;5(2):151-9 PMID: 1995413
  15. Wild-type but not mutant p53 immunopurified proteins bind to sequences adjacent to the SV40 origin of replication.
    Cell. 1991 Jun 14;65(6):1083-91 PMID: 1646078
  16. Adenovirus E1b-58kd tumor antigen and SV40 large tumor antigen are physically associated with the same 54 kd cellular protein in transformed cells.
    Cell. 1982 Feb;28(2):387-94 PMID: 6277513
  17. Association of human papillomavirus types 16 and 18 E6 proteins with p53.
    Science. 1990 Apr 6;248(4951):76-9 PMID: 2157286
  18. A DNA binding domain is contained in the C-terminus of wild type p53 protein.
    Nucleic Acids Res. 1991 Oct 11;19(19):5191-8 PMID: 1923804
  19. Presence of a potent transcription activating sequence in the p53 protein.
    Science. 1990 Aug 31;249(4972):1046-9 PMID: 2144363
  20. Monoclonal antibodies against simian virus 40 nuclear large T tumour antigen: epitope mapping, papova virus cross-reaction and cell surface staining.
    EMBO J. 1984 Jul;3(7):1485-91 PMID: 6204863
  21. Cellular immortalization by a cDNA clone encoding the transformation-associated phosphoprotein p53.
    Nature. 1984 Dec 13-19;312(5995):651-4 PMID: 6095117
  22. Evidence for allosteric variants of wild-type p53, a tumour suppressor protein.
    Br J Cancer. 1990 Apr;61(4):548-52 PMID: 2139577
  23. Precise epitope mapping of the murine transformation-associated protein, p53.
    EMBO J. 1985 Mar;4(3):699-706 PMID: 2408882
  24. p53 mutations in human cancers.
    Science. 1991 Jul 5;253(5015):49-53 PMID: 1905840
  25. Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life.
    Mol Cell Biol. 1988 Feb;8(2):531-9 PMID: 2832726
  26. Human wild-type p53 adopts a unique conformational and phosphorylation state in vivo during growth arrest of glioblastoma cells.
    Oncogene. 1992 Aug;7(8):1635-43 PMID: 1630823
  27. p53: a transdominant regulator of transcription whose function is ablated by mutations occurring in human cancer.
    EMBO J. 1992 Apr;11(4):1383-90 PMID: 1314165
  28. The p53 proto-oncogene can act as a suppressor of transformation.
    Cell. 1989 Jun 30;57(7):1083-93 PMID: 2525423
  29. Definition of a consensus binding site for p53.
    Nat Genet. 1992 Apr;1(1):45-9 PMID: 1301998
  30. Cooperation between gene encoding p53 tumour antigen and ras in cellular transformation.
    Nature. 1984 Dec 13-19;312(5995):649-51 PMID: 6390217
  31. Addition of fresh medium induces cell cycle and conformation changes in p53, a tumour suppressor protein.
    Oncogene. 1990 Nov;5(11):1683-90 PMID: 2176282
  32. Antibody-mediated activation of Drosophila heat shock factor in vitro.
    Science. 1990 Aug 3;249(4968):546-9 PMID: 2200124
  33. A single gene and a pseudogene for the cellular tumour antigen p53.
    Nature. 1983 Dec 8-14;306(5943):594-7 PMID: 6646235
  34. Participation of p53 cellular tumour antigen in transformation of normal embryonic cells.
    Nature. 1984 Dec 13-19;312(5995):646-9 PMID: 6095116
  35. Altered conformation of the p53 protein in myeloid leukemia cells and mitogen-stimulated normal blood cells.
    Oncogene. 1992 Aug;7(8):1645-7 PMID: 1630824
  36. Mammalian p53 can function as a transcription factor in yeast.
    Nucleic Acids Res. 1992 Apr 11;20(7):1539-45 PMID: 1579447
  37. Wild-type p53 activates transcription in vitro.
    Nature. 1992 Jul 2;358(6381):83-6 PMID: 1614538
  38. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas.
    Science. 1989 Apr 14;244(4901):217-21 PMID: 2649981
  39. A new anti-p53 monoclonal antibody, previously reported to be directed against the large T antigen of simian virus 40.
    Oncogene. 1987;1(4):453-5 PMID: 3330789
  40. Conformational analysis of p53 in resting and concanavalin A-stimulated mouse lymphocytes.
    Oncogene. 1992 Apr;7(4):661-6 PMID: 1565465
  41. A conformation hypothesis for the suppressor and promoter functions of p53 in cell growth control and in cancer.
    Proc Biol Sci. 1991 Aug 22;245(1313):139-45 PMID: 1682937
  42. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells.
    Cell. 1979 May;17(1):43-52 PMID: 222475
  43. Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form.
    EMBO J. 1990 May;9(5):1595-602 PMID: 1691710
  44. Application of a Theory of Enzyme Specificity to Protein Synthesis.
    Proc Natl Acad Sci U S A. 1958 Feb;44(2):98-104 PMID: 16590179
  45. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53.
    Cell. 1990 Dec 21;63(6):1129-36 PMID: 2175676
  46. Conditional inhibition of transformation and of cell proliferation by a temperature-sensitive mutant of p53.
    Cell. 1990 Aug 24;62(4):671-80 PMID: 2143698
  47. Determination of the c-MYC DNA-binding site.
    Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6162-6 PMID: 2068097
  48. Oncogenic forms of p53 inhibit p53-regulated gene expression.
    Science. 1992 May 8;256(5058):827-30 PMID: 1589764
  49. Monoclonal antibodies specific for simian virus 40 tumor antigens.
    J Virol. 1981 Sep;39(3):861-9 PMID: 6169844
  50. Tumor suppressor p53: analysis of wild-type and mutant p53 complexes.
    Mol Cell Biol. 1991 Jan;11(1):12-9 PMID: 1986215
  51. Identification of p53 as a sequence-specific DNA-binding protein.
    Science. 1991 Jun 21;252(5013):1708-11 PMID: 2047879
  52. Monoclonal antibody analysis of p53 expression in normal and transformed cells.
    J Virol. 1986 Aug;59(2):444-52 PMID: 2426467
  53. Oligomerization of oncoprotein p53.
    J Virol. 1988 Dec;62(12):4737-44 PMID: 3054153
  54. Cotranslation of activated mutant p53 with wild type drives the wild-type p53 protein into the mutant conformation.
    Cell. 1991 May 31;65(5):765-74 PMID: 2040013
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1993-03-00
Pages
1021-8
Language
English
Region
England
NLM ID
8208664
PMCID
PMC413303
Subset
IM
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2